Variant 7-150945175-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000238.4(KCNH2):c.*190C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 659,358 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00047 ( 1 hom. )

Consequence

KCNH2
NM_000238.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.02

Variant links:

Genes affected

KCNH2 (HGNC:6251): (potassium voltage-gated channel subfamily H member 2) This gene encodes a component of a voltage-activated potassium channel found in cardiac muscle, nerve cells, and microglia. Four copies of this protein interact with one copy of the KCNE2 protein to form a functional potassium channel. Mutations in this gene can cause long QT syndrome type 2 (LQT2). Transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, May 2022]

KCNH2 links:

KCNH2 (HGNC:):

KCNH2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 7-150945175-G-A is Benign according to our data. Variant chr7-150945175-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 910580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00352 (536/152330) while in subpopulation AFR AF= 0.0113 (471/41572). AF 95% confidence interval is 0.0105. There are 0 homozygotes in gnomad4. There are 251 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 536 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH2	NM_000238.4 linkuse as main transcript	c.*190C>T		3_prime_UTR_variant	15/15	ENST00000262186.10	NP_000229.1	Q12809-1Q15BH2A0A090N8Q0

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCNH2	ENST00000262186 linkuse as main transcript	c.*190C>T	3_prime_UTR_variant	15/15	1	NM_000238.4	ENSP00000262186.5	Q12809-1
KCNH2	ENST00000330883 linkuse as main transcript	c.*190C>T	3_prime_UTR_variant	11/11	1		ENSP00000328531.4	Q12809-2
KCNH2	ENST00000684241.1 linkuse as main transcript	n.4503C>T	non_coding_transcript_exon_variant	13/13

Frequencies

GnomAD3 genomes

AF:

0.00351

AC:

534

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00573

GnomAD4 exome

AF:

0.000473

AC:

240

AN:

507028

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

116

AN XY:

262124

show subpopulations

Gnomad4 AFR exome

AF:

0.00980

Gnomad4 AMR exome

AF:

0.00173

Gnomad4 ASJ exome

AF:

0.000216

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000341

Gnomad4 NFE exome

AF:

0.0000981

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00352

AC:

536

AN:

152330

Hom.:

Cov.:

AF XY:

0.00337

AC XY:

251

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0113

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00229

Hom.:

Bravo

AF:

0.00444

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2022	KCNH2: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 07, 2019	- -

Long QT syndrome 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over